Esters for synthesizing steroids



ESTERS FOR SYNTHESIZING STEROIDS Martin W. Farrar, Webster Groves, Harold Rafielson, St. Louis, and William S. Knowles, Kirkwood, Mo., assignors to Monsanto Chemical Company, St. Louis, Mo., a corporation of Delaware No Drawing. Original application July 23, 1953, Serial No. 369,944, now Patent No. 2,759,929, dated August 21, 1956. Divided and this application June 21, 1956, Serial No. 592,717 7 3 Claims. c1. 260-23955) from a 17 formyl-cyclopent 16 eno 10,13 dimethyl- A -decahydrophenanthren-3-one to a 17-(acyloxyacetyl) 17 hydroxy cyclopentano 10,13 --dimethyl- A dodecahydrophenanthren 3,11 dione. In particular this invention relates to methods and novel compounds useful in the preparation of acyl derivatives of 3,11,20- triketo-17,2l-dihydroxy-A -pregnene from a 3-keto-17- formyl-A androstatriene.

The sequence of steps or series of reactions proceed- I United States ing from a 17-fortnyl-cyclopent-16-eno-10,13-dimethy1- A decahydrophenanthrem3-one to a 17-(acyloxyacetyl) 17 hydroxycyclopentano 10,13 dimethyl- A -dodecahydrophenanthren-3,1l-dione essentially comprises (1) expoxidizing a l7-forrnyi-cyclopent-16-eno-10,

, 13-dimethyl-A -decahydrophenanthren-3 one with an clopentano 10,13 dimethyl A decahydrophenam,

thren-3-one so formed with a hypohalous acid, (8) oxidizing the 9,16-dihalo-1l,17-dihydroxy-17 (acyloxyacetyl) cyclopentano 10,13 dimethyl Afdodecahydrophenanthren-3-one with a complex of chromium oxide and a tertiary amine, (9) de-halogenating the 9,1 6-d h 1o 17 hydroxy 17 (acyloxyacetyl) cyclopentano 10, 13-dimethyl-A -dodecahydrophenanthren-3,1l-dione so as' to produce a 17-(acyloxyacetyl)-l7-hydroxy-cyclopen+ tano 10,13 dimethyl A dodecahydrophenanthren 3 ll-dione. The aforesaid sequence of steps is outlined schematically as follows: i

@cdan s CH0 7 0110 V o o o I 11 I In cmon ('JHN1 7 cmoR onion CHIOR i=0 0H 0H m1 HO Hal VIII Patented Nov. 4, 1958 This invention will be described in detail with, respect to its preferred embodiment but it is to be understood that such is not limitative of this invention.

The first step in the process of this invention is the epoxidation. of a 17-f0rmyl-cyclopent-16-eno-l0,l3-dimethyl-A -decahydrophenanthren 3-one to a 16,17- oxido 17 formyl cyclopentano 10,13 dimethyl A -decahydrophenanthren-3 one (Compound II) employing an oxygen furnishing agent such as the organic per-acids oihydrogen peroxide in an amount corresponding to approximately one chemical equivalent. The epoxidation is ordinarily carried out by mixing the oxidant and the 17 formyl cyclopent 16 eno 10,13 dimethy1-A %)edecahydrophenanthren-3-one together in an organic medium whichis non-reactive under the re-,

action conditions. Suitable media include chloroform, carbon tetrachloride, die'thyl ether, glacialacetic acid, methanol, ethanol, isopropanol, and the like. The temperature employed in the epoxidation may vary widely but ordinarily will be in the range of from about -10" C. to about 50 .C. A convenient reaction medium when the oxidant is hydrogen peroxide is a low molecularweight alcohol.

As illustrative of the first step of the process of this invention is the following: 7

Example I To a suitable reaction vessel containing 50'parts by weight (substantially 0.169 mol) of dl-3-keto-17-formyl- A -androstatriene (M. P. 178178.5 dissolved in 4200 parts by weight of methanol maintained at about C. is added approximately 170 parts by weight of sodium carbonate as a 5% aqueous solution followed by a methanol-hydrogen peroxide mix containing approxi mately 5.7 parts by weight of hydrogen peroxide. The mix so obtained is stirred for about 16 hours at about 0 C. T hereupon substantially all of the methanol is removed by vacuum distillation and the residue is then taken up with chloroform. The chloroform solution is then washed with water and dried over anhydrous magnesium sulfate. Upon evaporation of the chloroform there is obtained a white solid residue, which upon trative' of the preparation of a 3-keto-16,l7-oxido-1 7-carboxy-A 1 -androstadiene is the following: 7

Example II To an intimate mixture containing approximately 200 parts by weight of dioxane, approximately 192 parts by weight of 2.74 N sodium hydroxide, and approximately 44.6 parts by weight of silver nitrate is slowly added appioximately 40 parts by weight of dl-3-keto-16,17-oxidol7-formyl-A -androstadiene. Upon completion of the addition of the 16,17-oxido compound approximately 200 parts by weight of Water and approximately 200 parts by weight of dioxane is added with constant agitation.

- form. The chloroform extracts are combined, dried and native of the preparation of the acid halide (Compound Thereafter the mix is agitated for about one hour and is then filtered. The collected residue is washed with Water and the washings combined with the original filtrate. The aqueous layer is acidified and then extracted with chlorosubjected to vacuum distillation. Upon evaporation of the chloroform there is obtained a solid residue which upon triturating with diethyl ether yields 35 parts by weight of crystalline dl-3.-ke t o-16,17-oxido-l7-carboxy- A -androstadiene.

Similarly theindividual optically active isomers such as the natural .modification of 3-keto-16,17-oxido-l7-carboxy-A 9 -androstadiene are; obtained beginning with The next step inthe process of this invention the car-.

boxylic acid (Compound. III) is. converted to its acid halide (Compound IV) employing arpacyl halide forming agent such asoxalyl chloride-and thelike. As illus- LV) is the following:

Example 'III "To a solution containing approximately parts by Weight of a'l-3-keto-16,17-oxido-17-carboxy-A -androstadiene in approximately 4000 parts by weight of anhydrous methanol is added sufiicient sodium methylate to neutralize the epoxy acid. ,The methanol is removed by vacuum distillation and to the residue is added and intimately mixed about 450 parts by weight of benzene and about 2.5 parts by weight of pyridine followed by about 250 parts by weight of oxalyl chloride while maintaining the ,temperature at about 10 C. The mix so obtained is allowed to stand for about 30 minutes, whereupon the mix is subjected to vacuum distillation While maintaining the temperature at about 15 C. The residue is then taken up with about 500 parts by Weight of benzene and again subjected to vacuum distillation at a about 15 C. The residue is taken up with about 250 triturating with diethyl ether yields white crystalline 41-" conversion of the formyl $01115, i. e. the substituent in the 17-position, to a carboxy group (Compound III of the schematic diagram). This is readily brought about employing a mild oxidizing agent such as silver oxide, sodium chromate in acetic acid, and the like. As illusparts by weight of benzene and filtered. Upon subjecting the filtrate to vacuum distillation there is obtained the solid acid chloride of dl-3-keto-l6,17-oxido-17-carboxy- A -androstadiene.

Similarly the individual optically active isomers such as the acid chloride of the natural modification of 3-keto- 16,17-oxido l7-carboxy-A -androstadiene are obtained from the appropriate optically active isomer. 7

The next step in the process of this invention is the preparation of the diazoketone (Compound V) by react- "ing diazomethane with an acid halide of a 16,17-oxidodecahydrophenanthren-3-one.

1'] carboxy cyclo pentano 10, 13 -dimethyl A Ordinarily an excess of two chemical equivalents of diazomethane i employed in converting the acid halide (Compound IV) to the diazoketone (Compound V) and in general the process is carried out in an.inert organic solvent such as diethyl ether, benzene, dioxane, toluene, etc., at a temperature in the range of 20 to 40)? C. As illustrative of the preparation of thediazoketone is the following:

Example IV To a suitable reaction vessel containing an ether solution cdntaining 100 parts by Weight of diazomethane' is added approximately 50 parts by weight of the acid chlo ride of dl- 3-keto-16,17-oxido:i7-carboxy-Ah Landfostadiene dissolved in 500 parts by weight of benzene while maintaining the temperature at about C. The mixture so obtained is then agitated for about one hour at about 0 C. The mix isthen subjected to vacuum distillation to remove the solvents whereupon there is obtained yellow crystalline dl-3,20-diketo-16,l7 oxido-2l-diazo- A -pregnadierie. Y

Similarly the individual optically active isomers such as the natural modification of 3,20-'diketo-16,17-oxido-2ldiazo-A -pregnadiene are, obtained. beginning with the acid halide'of the appropriate'optica'lly active isomer of 3-keto-16,l7-oxido-l7-carboxy-A -androstadiene.

The next step in the process of this invention is the formation of the 17-(acyloxyacetyl)-16,17-0xido-cyclopentano 10,13 dimethyl- A decahydrophenanthren-3-on'e (Compound 'VI)" from the diazoketone (Compound V) by heating the latter in the presence of a monocarboxylic acid such as acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, lauric acid, stearic acid, phenylacetic acid, fi-phenylpropionic acid, benzoic acid, toluic acid, etc., in the presence where desirable of an inert organic solvent such as benzene, toluene, xlyene, dioxane, etc. It is preferred'th'at the carboxylic acid be a fatty acid and preferably one containing from 2 to .4 carbon atoms. As illustrative of this step is the follow- Example V To a suitable reactionvessel containing approximately 5000 parts by weight of acetic acid is added approximately 50 parts by weight of dl-3,20-diketo-16,17-oxido- 21 diazo-M'? -pregnadiene and the mix so "obtained heated at about 9095 C. for about 30 minutes. The resultant mix is then subjected to vacuum distillation and the residue so obtained taken up with chloroform. The chloroform solution is then washed with aqueous sodium bicarbonate, then with water and finally dried. Upon removal of the solvent there is obtained solid dl-3,20-diketo-l6,17-oxido-21-acetyloxy-A -pregnadiene in the form of white crystals. Similarly the individual optically active isomers such as the natural modification of 3,20-diketo-16,17-oxido-2lacetyloxy-A -pregnadiene are obtained from the appropriate optically active isomer of 3,20-diketo-16,17- oxido-Zl-diazo-A -pregnadiene.

The next step of the process of this invention is the opening of the epoxide grouping by reacting the 17- (acyloxyacetyl) 16,17 oxido cyclopentano 10,13- dimethyl A4361) decahydrophenanthren 3 one (Compound VI) with a hydrogen halide such as HCl, HBr, or HI which results in the formation of a halohydrin (Compound VII), namely 16-halo-17-hydroxy-l7- (acyloxyacetyl) cyclopentano 10,13 dimethyl- A -decahydrophenanthren-3-one. This reaction is preferably carried out in an inert organic solvent containing dissolved therein the hydrogen halide reactant and at a temperature in the range of about 20 C. to about 40 C. As illustrative of this step is the following:

Example VI Approximately 40 parts by weight of dl-3,20-diketo- 16,l7-oxido-2l-acetyloxy-A -pregnadiene is admixed with approximately 3000 parts by weight of acetic acid and approximately 1000 parts by weight of benzene in a suitable reaction vessel. 'I'hereto is added while maintaining the temperature at about 0 C. approximately 80 parts by weight of a 38% acetic acid solution of hydrogen bromide and the mix so obtained agitated for about minutes at about 0 C. To the mix is then added an equal volume of Water and the composite so obtained extracted with several small portions of chloroform. The chloroform extractsare combined, washed with water and dried over anhydrous magnesium sulfate. Upon subjecting the so dried solution to vacuum distillation in order to remove the chloroformthere is obtained white crystalline dl-3,20-diketo-16 8-bromo-17oi-hydroxy+ 21-acetyloxy-A -pregnadiene;

In a similar fashion but employing hydrogen chloride instead of hydrogen bromide white crystalline dl-3,20-

diketo 16,8 chloro 17oz} hydroxy 21 acetyloxy-' A -pregnadicne is obtained from dl3, 20-diketo-16,17- oxide-21-acetyloxy-A -pregnadiene.

Similarly the'individual optically active isomers'suc as the natural modification of 3,20-diketo-16fi-bromo-17mhydroxy-21-acetyloxy-A D-pregnadiene are' obtained from the appropriate optically active isomer of 3,20-

diketo-16, 17-oxido-2 l-acetyloxy-A -pregnadiene.s

The next step in the process of this invention is the reacting of the 16-halo-17-hydroxy compound (Compound VII) with a hypohalous acid to form the 9,16- dihalo 11,17 dihydroxy 17.- (acyloxyacetyl) cyclopentano 10,13 dimethyl A dodecahydrophenanthren-3-one (Compound VIII). The addition reaction is brought about by mixing a solution of a hypohalous acid, preferably hypobromous acid, with a solution of a 16- halo 17 hydroxy 17 (acyloxyacetyl) cyclopentano- 10,13-diruethyl-A -decahydrophenanthren-3-one at a temperature in the range of about 0 to 30 C. The 9-halo and ll-hydroxy substituents so introduced bear a trans relationship to one another, that is one occupies the plane above ring C While the other occupies the plane below ring C, however, it is to be understood that the element of this invention is not limited'to any assumption as to chemical structure butpertains broadly to the 9-halo-11- hydroxy addition product of a hypohalous acid and a 16 halo 17 hydroxy 17 (acyloxyacetyl) cyclo-.

pentano 10,13 -'dimethyl A4901) decahydrophenanthren-B-one (Compound VII). Various solvents which are'inert under conditions of the addition reaction may be used in the preparation of the 9-halo-11-hydroxy addition product (Compound 'VIII), for example acetone,

NBr

CHzC

in a suitable inert organic solvent, e. g, acetone, tertiary butanol, with water and a small amount of sulfuric acid,

Where desired, the hypobromous acid solution can be prepared first and then mixed with 16-halo-17-hydroxy- 17 (acyloxyacetyl) cyclopentano 10,13 dimethyl- A decahydrophenanthren-3-one (Compound VII) or, preferably, the hypobromous acid is prepared in the presence of the reactant (i. e. Compound VII) so that the elements of hypobromous acid add to the 9-11 double bond as soon as they are formed. As illustrative of this step of the process of this invention employing hypobromous acid is the following:

Example VII To an agitating solution containing substantially 63 parts by weight of dl-3,20-di keto-16fi-bromo-l7m-hydroxy 21 acetyloxy A4501) pregnadiene, substantially 2800 parts by weight of acetone and substantially;

1200 parts by weight of water is added atabout 5 C.

approximately'50 parts by weight oif 1 N sulfuric acid. To the so cooled and acidified solution is slowlyadded a solution c'orit'a ining substantially 35 ,parts by weight of N-bromo-succinimide in approximately 360 parts by Weight of acetone, Upon completion of the Nbromosuccinimide'addition the mix is agitated forabout hours at about 0-5 C the bronio-hydrin crystallizes fromdthe solution duringthe-agitation. -At the end'ofl the agitation period aqueous sodium sulfite is added to destroy the excess N-bromo-succ iriirnide and then the mix is neutraliz ed with sodium bicarbonate. The 'mix is then filtered and theresidue washed first with water, then with acetone and-dried. The white crystalline product so obtained is dl 3,20 diketo 90;,176 dibr0mo 115,176; dihydroxy-2l-acetyloxy-A -pregnene.

In a similar fashion beginning with dl-3,20-diketo- 16B chloro 17cc -j .'hydrox-y 2'1 acetyloxy A4,9(11)- pregnadiene white chystalline dl-3,20-diketo-9a-bromo 16,8 chloro 115,170: dihydroxy 21 acetyloxy A preg nen'e is obtained.

all 3,20 diketo 9u,-l 6[3 dichloro 11,8,1711 dihydroxy-2l-acetyloxy-M-pregnene may be prepared by admixing the '9 -bromo-11B-hydroxy compound (i. e. the product of Example VII) with a small amount of potass'ium acetate and boiling the mix in alcohol to effect formation of the 9 11, 16-17 dioxido derivative, the dioxido compound so obtained upon reacting with hydrochloric acid in chloroform at about 0-5 C. yields dl- 3,20 diketo 9m, 16/8 dichloro 1l 8,17m dihydroxy- 2'l-acetyloxyA -pregnene. V Similarly the individual optically active isomers of 3,20- diketo 90:,16 8 -'dihalo 115,170 dihydroxy 4 21 acetyloxy A -pregnene, e. g. the natural modification of 3,20- diketo 911,165 dibromo 11B,l7a dihydroxy a 21- acetyloxy-M-pregnene are obtained from the appropriate optically active 3,20- diketo-l6fi halo-l-7a-hydroxy-2lacetyloxy-A hpregnadiene. V

The next step in the process of this invention is the oxidation of the ll-hydroxy substituent of Compound VIII of the foregoing schematic diagram to produce the 16.-halo 17 hydroxy-17-(acyloxyacetyl)-cyclopentano- 9-halo 10,13 dimethyl A dodecahydrophenanthren- 3,11-dione (Compound IX) O Halogen I where x is a halogen atom such as bromine, chlorine and onion o='o iodine and where R is an acyl radical derived from a hydrocarbon monocarboxylic acid. This oxidation step is brought about in an anhydrous system by mixing a complex of chromium oxide'and a tertiary amine, such as pyridine or the variouspicolines, etc., with the 9-haloll-hydroxy compound (Compound VIII). As illustrative of this step of the process of this invention is the following:

Example VIII To an agitated complex of chromium trioxide and pyridine prepared in the cold by admixing 50 parts by weight of chromium trioxide with 500 parts by weight of pyridine is added substantially 50 parts by weight of dl-3,20-diketo 9,16 dibromo 11,8,17u dihydroxy-Zlacetyloxy-A pregn'ene in approximately 800 parts by weight of-pyridine while maintaining the temperature at about 10 C. 'The mixture so obtained is permitted to stand :atro'o'm temperature for about 16 hours with occasional agitation. The mixture is then filteredand the residue washed with ,p'yridine. The'pyridine wash and the {angi a filtrate are combined and the solution so formediisupoured 'in tofi ve times'its weight of water and thelcompos it extracted with chloroform. 'The extracts are combined and cooled to about 0 C. The cooled solution is then washed with dilute hydrochloric acid and then with water. Theorganic layer is recovered, dried, and evaporatedf to dryness- The residue is white. crystalline dl-3, 1l, 20-triketo 90:,166 dibroino-17a-liydroxy-Zl-acetyloxy-M-pregnene Replacing dl-3g2o-diketo-9a,l6fl-dibi'omo 11B,17a-dihy-, droxy-2l-acetyloxy-h -pregnene in Example VIII with an equal weight of 'dl 3g'2o-diketo-9a,l6 3-dichloro-11 3,17- dihydroxy-Zl-acetyloxy- =pregnene and subjecting same to the series of steps se't'forth in Example VlIl nil-3,11,20-

-triketo-9a,16 3-dicliloro 1711'- hydroxy-21acetyloxy A pregnene is obtained. I I p In a similar fashion the individual optically active; iso-. mers of 3 1 1, 2O tr iketo 9 a, l6fl-diha lo-17a-hydroxy 21- acet'yloxy A -ipregnene, e.' g. the natural modification of 3 ll ,20-'triketo'-9cg l 6B-dibromo-l7a hydroxy-2 l-acetyloxy-A -pregnene'is obtained .from the appropriate optically active 3,20-diketo-9a,l6/3-dihalo-11/8,l7a-dihydroxy- 2l-acetYloxy-M-pregnene. V y

The next step in the process of this invention isihe removal ofthe 9-halogen and lfi-halogen substituents on the 16-halo 1 7 hydroxy-17-(acyloxyacetyl)-cyclopentano 9 -ha'lo 10,1'3 -'dimethyl A dodecahydrophenanthren 3,11-dione. I 9-position is removed first toprovide a l6-halo-l7-hydroxy-17-(acyloxyacetyl) cyclopentano-10,13-dimethyl- A -dodecahydrophenanthren-3,1l-dione (Compound X) which compound upon =dehalogenating produces a l' 7.- hydroxy l7 '(acyloxyacetyl)-cyclopentano 10, 13 dimethyI A -dodecahydrophenanthren 43,11 dione (Conn. pound XI). :It isv preferred to remove both halogen sub stituents in one operation and as illustrative of this enrploying a large excess of Raney nickel is the following:

Example IX 7 1 To a "suitable reaction vessel containing 20 par-ts by weight of Raney nickel, approximately 200"parts by weight of-acetone and about 20 parts by weight of water is added approximately 3.5 parts by weight of dl-3,l1,20- triketo 91516;? -dibrom0 17oz hydroxy-21-acetyloxy- A -.pregnene and the mixture so obtained refluxed in'an atmosphere of nitrogen for about 4 hours. The reaction mix 'is then filtered and the residue washed with warm acetone. The washings and original filtrate are combined and subjected to vacuum-distillation. The residue is then taken 'up with chloroform and the solution so formed washed with water and dried. The dried 'solutionis then subjected to vacuum distillation whereupon there is obtained white crystalline dl-3,11,20-'triketo-17ahydroxy-2l-acetyloxy-A pregnene (M. 'P. 240-243 C.) which compound is identical with the acetate of rac'emic (dl) cortisone. V 7

Similarly the individual optically active isomers such as the natural modification (dextro-rotatory form) of 3,11,20-triketo=17a hydroxy '21 acetyloxy-A -preg'nene are obtained beginning with the appropriate optically active isomers of 3,11,20-triketo-9u,l6B-dibromo-l7a-hydroxy-2l-acetyloxy-A -pregnene. The 21-acyl derivative of the "natural modification of 3,ll,20-triketo-l7a,2l'-dihydroxy-A -pregnene according to infrared spectrum, melting point and optical. rotation 'is identical with the corresponding acyl derivative of natural cortisone. Thus- 7 I 1y, it is to ;be understood that the-optically active isomers In this step the halogen substituent in the (acyloxyacetyl) cyclopentano 10,13 dimethyl-A decahydrophenanthren 3 one compound (Compound VH) was employed to prepare the 9-halo-1l-hydroxy addition product (Compound VIII) it has been found that it (i. e. Compound VII) upon dehalogenating provides for a 17-hydroxy-17-(acyloxyacetyl)-cyclopentano- 10,13-dimethyl A' decahydrophenanthren 3 one which compound upon reacting with a hypohalous acid produces a 9-halo-l1-hydroxy addition product which addition product upon dehalogenating yields a 11,17- dihydroxy 17 (acyloxyacetyl) cyclopentano-10,l3-dimethyl A dodecahydrophenanthren 3 one. This sequence of steps is outlined schematically as follows, R and 2: having the same significance as aforedescribed.

a. trsfi ga As illustrative these steps proceeding from Compound VI! to Compounds XII and XIII and finally to Compound XIV is the following:

Example X To a suitable reaction vessel containing 10 parts by weight of Raney nickel, approximately 100 parts by weight of acetone and about 10 parts by weight of water is added and intimately mixed 3 parts by weight of d!- 3,20 diketo 16B bromo 17oz hydroxy 21-acetyloxy- A -pregnadiene and the mixture so obtained refluxed in an atmosphere of nitrogen for about 4 hours. The reaction mix is then filtered and the residue washed with warm acetone. The washings and original filtrate are combined and subjected to vacuum distillation. The residue is then taken up with chloroform and the solution so formed washed with water and dried. The dried solution is then subjected to vacuum distillation whereupon there is obtained white crystalline dl-3,20-diketo-17-hydroxy-21- acetyloxy-A -pregnadiene.

Similarly the individual optically active isomers such as the natural modification of 3,20-diketo-17a-hydroxy-2lacetyloxy-A -pregnadiene are obtained beginning with the appropriate optically active isomer of 3,20-diketo-165- bromo-l7a-hydroxy-21 acetyloxy A4901) pregnadiene.

The natural modification or dextro-rotatory form of 3,20-

diketo-lh-hydroxy-Zl acetyloxy A4301) pregnadiene possesses a melting point of 233-236 C.

The aforedescribed dl-3,20-diketo-l7a-hydroxy-2l-acetyloxy-5 -pregnadiene upon reacting with a hypohalous acid such as hypobromous acid in accordance with the process of Example VII produces white crystalline dl- 3,20-diketo-9u-bromo-1 1 B, 17 a-dihydroxy-21-acetyloxy-A pregnene which 9-bromo-1l-hydroxy addition product upon dehalogenating using Raney nickel provides for til-3,20 diketo-115,17a-dihydroxy-2l-acetyloxy-A pregnene which compound has the same infrared spectrum as the (21-) acetate of 17-hydroxy corticosterone. Similarly but beginning with the natural modification of 3,20-diketo-17ahydroxy-2l-acetyloxy-A -pregnadiene the acetate obtained is identical with the (21-) acetate of 17-hydroxy corticosterone.

The natural modification of 3-keto-16,17-oxido-17- formyl-A -androstadiene referred to in col. 3, lines 641T, is a white crystalline substance melting at 193-197 C. The natural modification of 3-keto-16,17-oxido-1'lcarboxy-A -androstadiene referred to in col. 4, lines 241i, is a white crystalline substance melting at 2ll-212 C. The natural modification of 3,20-diketo-16,17-oxido- 2l-diazo-A -pregnadiene referred to in col. 5, lines 111i, is a yellow crystalline substance melting at -168 C. The natural modification of 3,20-diketo-16p-bromo- 17a-hydroxy-21acetyloxy-A -pregnadiene referred to in col. 6, lines 111i, is a White crystalline substance melting at 146448" C.

This application is a division of co-pending application Serial No. 369,944, filed July 23, 1953, now U. S. Patent No. 2,759,929.

While this invention has been described with respect to certain embodiments it is not so limited and it is to be understood that variations and modifications thereof obvious to those skilled in the art may be made without departing from the spirit or scope of this invention.

What is claimed is:

1. 16,17-oxido-17-(acyloxyacetyl)-cyclopentano-10,13- dimethyl-A -decahydrophenanthren-B-one l I .Q

where R is an acyl radical obtained from a hydrocarbon carboxylic acid of the structure hydrocarbon-O-OH upon removal of the ---OH group from said hydrocarbon carboxylic acid.

2. The compound of claim 1 wherein R is an acyl radical obtained from a fatty acid containing 2 to 4 carbon atoms upon removal of the OH group thereof.

3. 3,20-diketo 16,17 oxide-21acetyloxy-A -pregnadiene.

References Cited in the file of this patent UNITED STATES PATENTS 2,602,769 Murray et al July 8, 1952 2,649,402 Murray et a1. Aug. 18, 1953 2,705,711 Dodson' Apr. 5, 1955' 

1. 16,17-OXIO-17-(ACYLOXYACETYL)-CYCLOPHENTANO-10,13DIMETHYL-$4,9(11) -DECAHYDROPHENANTHREN-3-ONE 